Sand Jannie M B, Martinez Gerd, Midjord Anne-Kirsten, Karsdal Morten A, Leeming Diana J, Lange Peter
Nordic Bioscience, Biomarkers and Research, Herlev, Denmark; Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Section of Respiratory Medicine, Hvidovre Hospital, Hvidovre, Denmark.
Clin Biochem. 2016 Oct;49(15):1144-1151. doi: 10.1016/j.clinbiochem.2016.09.003. Epub 2016 Sep 7.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been associated with exacerbations of COPD. However, characterization of these in individuals with clinically stable COPD is lacking. The aim of this study was to characterize the collagen remodeling in stable COPD by the serological assessment of neo-epitopes.
Sixty-eight subjects with clinically stable COPD were included into the study at baseline, and 27 came back for a four weeks follow-up visit. Serum and plasma levels of neo-epitopes were assessed for the evaluation of collagen type III (C3M), IV (C4M, C4Ma3, P4NP 7S), and VI (C6M, Pro-C6) remodeling.
C3M, C4M, C4Ma3, P4NP 7S, and C6M levels were significantly elevated in COPD subjects compared with healthy controls (p<0.0001 to p=0.044). Each neo-epitope biomarker was significantly correlated between serum and plasma (p<0.0001) and most biomarkers were stable in the majority of patients from baseline to week four. Serum C6M levels were weakly correlated with FEV% predicted (r=-0.274, p=0.025) and serum Pro-C6 levels were elevated in subjects with previous exacerbations (p=0.014). C3M, C4Ma3, C6M, and P4NP 7S were weakly correlated with MRC dyspnea scores (p<0.01). No associations were seen with BMI, smoking, duration of COPD, blood oxygen saturation, shuttle walk test distance, GOLD grades, or CAT scores.
Serological biomarkers of collagen remodeling were elevated in subjects with COPD as compared with healthy individuals. Biomarker levels were significantly correlated with measures of dyspnea, indicating a relationship with degree of symptoms, while only C6M showed a weak but significant association with lung function. Biomarker levels were not related to GOLD grades, which was in line with previous studies indicating that ECM remodeling may be related to disease activity rather than severity.
慢性阻塞性肺疾病（COPD）的特征是慢性炎症导致肺细胞外基质（ECM）过度重塑，从而使蛋白质片段（新表位）释放到血液中。此前评估这一情况的血清学标志物已被证实与COPD急性加重相关。然而，对于临床稳定的COPD患者中这些标志物的特征描述尚缺乏。本研究的目的是通过对新表位的血清学评估来描述稳定期COPD患者的胶原重塑情况。
68例临床稳定的COPD患者在基线时纳入本研究，27例患者进行了为期四周的随访。评估血清和血浆中新表位水平，以评价III型（C3M）、IV型（C4M、C4Ma3、P4NP 7S）和VI型（C6M、Pro-C6）胶原重塑情况。
与健康对照组相比，COPD患者的C3M、C4M、C4Ma3、P4NP 7S和C6M水平显著升高（p<0.0001至p=0.044）。每种新表位生物标志物在血清和血浆之间均显著相关（p<0.0001），并且大多数生物标志物在大多数患者中从基线到第四周保持稳定。血清C6M水平与预测的FEV%呈弱相关（r=-0.274，p=0.025），既往有急性加重史的患者血清Pro-C6水平升高（p=0.014）。C3M、C4Ma3、C6M和P4NP 7S与MRC呼吸困难评分呈弱相关（p<0.01）。未发现与BMI、吸烟、COPD病程、血氧饱和度、往返步行试验距离、GOLD分级或CAT评分存在关联。
与健康个体相比，COPD患者胶原重塑的血清学生物标志物升高。生物标志物水平与呼吸困难程度显著相关，表明与症状严重程度有关，而只有C6M与肺功能呈弱但显著的关联。生物标志物水平与GOLD分级无关，这与先前的研究一致，表明ECM重塑可能与疾病活动度而非严重程度相关。
